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An et al. Hepatoma Res 2023;9:43 https://dx.doi.org/10.20517/2394-5079.2023.60 Page 3 of 12

life of 64.2 hours. Tumor necrosis is mediated by irreversible DNA damage caused by oxygen free radicals
generated by the beta radiation emitted by the radioactive microspheres. The radiation emitted by the
microspheres penetrates approximately 2.5 mm into the surrounding tissues, minimizing non-target
radiation exposure beyond microsphere deposition within tumor [20,21] .

While the goal of TARE is to selectively deliver high doses of radiation to tumors, there is a risk of non-
90
target radioactive microsphere deposition and associated side effects. The anticipated distribution of Y
microspheres may be assessed with a “mapping” angiogram prior to treatment . During the mapping
[22]
procedure, Technicium-macroaggregated albumin is delivered trans-arterially to the vessels supplying the
99m
tumor, and SPECT-CT is performed to assess the distribution. In addition, extrahepatic vessels with
potential communication with the tumoral vessels are also interrogated and may be embolized if necessary
9m
90
to prevent non-target radiation. Tc-MAA particles and Y microspheres are approximately the same size,
so the distribution of injected Tc-MAA may be used as a surrogate for the radiation treatment dose
9m
distribution.
Non-target deposition of radioactive microspheres to the lungs or gastrointestinal tract may result in
radiation pneumonitis or enteritis [23-25] . The mapping procedure performed with Tc-MAA prior to
99m
treatment allows for quantification of potential non-target microsphere deposition to the lungs and bowel
and adjustments to the dose administration to limit the potential for radiation-induced complications. The
mapping procedure is typically performed 1 to 2 weeks prior to the later radioembolization procedure. In
Figure 1, the lung shunt fraction is being assessed following a mapping procedure prior to TARE treatment
of a right-sided intrahepatic cholangiocarcinoma. In addition, the mapping procedure helps define the
appropriate radiation dose to deliver to the tumor.

In Figure 2, we show illustrative images of the TARE workflow from an example patient who presented with
a large left-sided intrahepatic cholangiocarcinoma occupying the entirety of the left lobe with extension into
the right lobe and involving the porta hepatis.

Clinical efficacy of TARE
TARE has demonstrated clinical efficacy in the setting of unresectable intrahepatic cholangiocarcinoma.
Median overall survival has been reported between 9.3 and 22 months following TARE for unresectable
intrahepatic cholangiocarcinoma in several retrospective studies [26-31] . A 2015 meta-analysis with 298 patients
who underwent TARE for unresectable intrahepatic cholangiocarcinoma demonstrated a median survival of
[32]
15.5 months with a 3-month partial response rate of 28% and a stable disease rate of 54% . Similarly, a
study by Hoffman et al. reported partial response in 36% of patients and stable disease in 52% of patients at
3-month follow-up post TARE . Increased overall survival post TARE was associated with ECOG
[29]
performance status of 0 to 1, increased radiation treatment dose, and evidence of tumor response on
imaging post treatment [27,29] . A summary of studies examining TARE for intrahepatic cholangiocarcinoma is
included in Table 1. Factors associated with poor survival post TARE included impaired liver function
(elevated INR and bilirubin), elevated MELD post treatment, and increased time from diagnosis to TARE
treatment .
[33]
Patients who undergo TARE for unresectable intrahepatic cholangiocarcinoma are sometimes able to be
down-staged to surgical resection post-treatment. Mouli et al. studied 46 patients who underwent TARE for
unresectable intrahepatic cholangiocarcinoma and found that 5/46 (11%) were able to qualify for surgical
resection due to partial treatment response following TARE . Patients who can be down-staged to surgical
[34]
resection post TARE have a significant survival benefit, with a study by Bourien et al. demonstrating a